We contributed to several mouse studies of the role of genetic differences in responses to environmental agents. Compared to normal mice, we found that mice that express higher levels of the NAG-1 gene (nonsteroidal anti-inflammatory drug-activated gene, an anti-cancer gene) have a less body fat. In addition, the NAG-1 mice have less inflammation when exposed to a systemic inflammatory agent, lipopolysaccharides (LPS). This lower body fat and inflammation response may help explain the mechanism for why these mice also have lower rates of cancer. In another mouse study, we compared normal mice to mice lacking one of the estrogen receptors. The mice lacking the estrogen receptor tend to be less fertile than normal mice, but the mechanism for the reduced fertility is not known. We found that among the organs involved in fertility, only the ovaries are affected by absence of the receptor and that they do not produce adequate levels of hormones to stimulate ovulation. In addition to these studies of genetic differences, we also investigated a new assay of a functional aspect of mitochondria (mitochondrial respiration) using rat liver. Because mitochondria provide energy to the cell, it is important that its function is not impaired by environmental agents. We evaluated this assay using known inhibitors of mitochondrial function, along with a range of perfluoroalkane chemicals. We were able to show that mitochondrial respiration was greatly reduced by known inhibitors, indicating that the assay was operating well, and that respiration was differentially affected by the perfluoroalkane chemicals in a manner associated with their molecular size and composition. Finally, we studied behavioral differences between male and female rats that were treated with estrogenic compounds during gestation and after birth until weaning. There were a number of behavioral and physical effects of these compounds, with females more affected than males.